Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI, USA.
Center for Biomedical Engineering, Brown University, Providence, RI, USA.
Adv Exp Med Biol. 2018;1092:69-90. doi: 10.1007/978-3-319-95294-9_5.
The microenvironment in a solid tumor includes a multitude of cell types, matrix proteins, and growth factors that profoundly influence cancer cell mechanics by providing both physical and chemical stimulation. This tumor microenvironment, which is both dynamic and heterogeneous in nature, plays a critical role in cancer progression from the growth of the primary tumor to the development of metastatic and drug-resistant tumors. This chapter provides an overview of the biophysical tools used to study cancer cell mechanics and mechanical changes in the tumor microenvironment at different stages of cancer progression, including growth of the primary tumor, local invasion, and metastasis. Quantitative single cell biophysical analysis of intracellular mechanics, cell traction forces, and cell motility can easily be combined with analysis of critical cell fate processes, including adhesion, proliferation, and drug resistance, to determine how changes in mechanics contribute to cancer progression. This biophysical approach can be used to systematically investigate the parameters in the tumor that control cancer cell interactions with the stroma and to identify specific conditions that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer. Increased understanding of the underlying biophysical mechanisms that drive cancer progression may provide insight into novel therapeutic approaches in the fight against cancer.
肿瘤的微环境包含多种细胞类型、基质蛋白和生长因子，这些物质通过提供物理和化学刺激，深刻地影响着癌细胞的力学特性。这种肿瘤微环境本质上是动态和异质的，在癌症进展过程中起着关键作用，从原发性肿瘤的生长到转移性和耐药性肿瘤的发展。本章概述了用于研究癌症细胞力学和肿瘤微环境在癌症进展不同阶段（包括原发性肿瘤生长、局部侵袭和转移）中力学变化的生物物理工具。通过对细胞内力学、细胞牵引力和细胞迁移的定量单细胞生物物理分析，很容易将其与关键细胞命运过程（包括黏附、增殖和耐药性）的分析相结合，以确定力学变化如何促进癌症进展。这种生物物理方法可用于系统地研究控制癌细胞与基质相互作用的肿瘤参数，并确定诱导促进肿瘤行为的具体条件，以及抑制这些条件的治疗癌症的策略。深入了解推动癌症进展的潜在生物物理机制，可能为抗击癌症提供新的治疗方法。
